The proportion of users of sweet-flavored and mentholated tobacco products has increased dramatically, especially among adolescents, raising concerns that flavors may facilitate tobacco product initiation and promote nicotine addiction. An additional concern is the recent introduction of synthetic cooling agents that may have effects similar to menthol. Children and adolescents are conditioned, through prior experience, to associate sweet and cooling flavors (fruit, candy, mints, etc.) with high sweetener content (sugar or artificial sweeteners). However, the role of flavors in the initiation of tobacco product use is difficult to study in humans, especially in adolescents and never-users. The goal of this project is to use adolescent and adult rodent models of inhaled and smokeless tobacco product use, and of oral flavor-paired nicotine self-administration, to examine whether sweet and cooling flavors in tobacco products enhance nicotine use behavior and addiction. Researchers will determine whether early flavor exposure and early flavorant associations with sweeteners influence subsequent nicotine choice and initiation, maintenance, and relapse. Study aims are: (1) to examine sweet and cooling flavor exposure and conditioning effects on nicotine choice and use using the two-bottle choice test in mice and nicotine self-administration in rats; and (2) to examine the effects of synthetic cooling agents on respiratory irritation caused by e-cigarette vapors. Study findings will provide new information about sweet and cooling flavor effects on the initiation and persistence of tobacco use.